Temporomandibular disorders (TMD) to a family of conditions that cause pain of the temporomandibular joint (TMJ) region and surrounding deep craniofacial muscles. Although the etiology of TMD's may vary, this facial pain condition is commonly accompanied by long-term changes in sensory, motor reflex and autonomic function suggesting a central dysfunction. TMD is notable for its higher prevalence in women than in men and for its recurrent nature. Despite evidence for an underlying central neural dysfunction, little is known of the brain mechanisms necessary for TMD pain. The central hypothesis of this proposal is that sex-related differences in TMD pain reside, at least in part, at the level of second-order neurons within the spinal trigeminal nucleus and upper cervical dorsal horn. Since the neurons that supply the tissues of the TMJ region terminate in the trigeminal brainstem complex and upper cervical spinal cord, the activity of second-order neurons within these regions must assume a critical importance in determining the various aspects of nociception (e.g., sensory-discrimination, autonomic reflexes, recruitment of descending controls). The proposed studies use an animal model to selectively activate small diameter afferent nerves and converging methodologies (c-fos) immunocytochemistry, in vivo microdialysis, single neuron electrophysiology) to examine the properties of second-order neurons that receive noxious sensory input from the TMJ region in anesthetized male and female rats. The Specific Aims examine the effects of the well-known activators of endogenous pain control systems, morphine and vagal afferent nerve activity, to assess the properties of TMJ-responsive neurons in male and female rats. The long-term goal of this research is to better understand the influences of brain-endocrine-autonomic interactions in orofacial pain processing. The shorter term goal is to define the involvement of opiate and vagal afferent nerve mechanisms at the level of the trigeminal brainstem complex that may have analgesic effects after inflammation of the TMJ region.